Article Text

P183 Urea induced ros accelerate renal failure progression
  1. Maria D’Apolito1,
  2. Anna Laura Colia2,
  3. Roberta Caggianello1,
  4. Massimo Pettoello-Mantovani3,
  5. Michael Brownlee4,
  6. Angela Bruna Maffione2,
  7. Ida Giardino2
  1. 1Paediatric Research Centre, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
  2. 2Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy
  3. 3Pediatric Research Centre, University of Foggia, Scientific Institute ‘Casa Sollievo della Sofferenza’, Foggia, Italy
  4. 4Diabetes Research Centre, Albert Einstein College of Medicine, New York, USA


Background and aims Chronic kidney disease (CKD) in children is an irreversible process that may lead to end-stage renal disease (ESRD). Uremic toxins have been suggested to promote progression of chronic renal failure. Urea has been long considered to have negligible toxicity in patients with CKD. In contrast, a consistent number of in vitro and in vivo studies have recently shown a direct toxicity of urea. Here we investigate the hypothesis that concentrations of urea associated with CKD and increased ROS production in adipocytes and endothelial cells might also increase ROS production directly in human podocytes, causing abnormalities which promote the progression of kidney damages

Methods Human conditionally immortalised podocytes were cultured in the presence or absence of 20 mM urea.

Results Urea at concentrations usually seen in CKD, induce mitochondrial ROS production in cultured human podocytes, leading to cellular dysfunctions typically seen in the CKD progression. Urea induced ROS decrease nephrin and podocine expression (markers of renal function), increase p65 and MCP-1 expression (markers of inflammation), and increase the intracellular lipid synthesis, as shown by the increased expression and activity of the transcription factor SERBP1. Normalisation of mitochondrial ROS production prevents each of these effects of urea. In uremic mice, treatment with MnTBAP prevents the progression of renal failure.

Conclusions Taken together, these data suggest that urea itself contributes to the progression of renal failure Since urea’s effects are caused by its capacity to induce mitochondrial ROS production, reduction in the high morbidity and mortality caused by ESRD may be achieved by novel therapeutics that directly target urea-induced ROS.

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